title: Epistatic interactions and drug response.
abstract: The advent of massively parallel sequencing has allowed for an unprecedented genetic characterization of cancers, which has revealed not only the complexity of cancer genomes, but also the fact that tumours from the same anatomical site or even of the same histological and/or molecular subtype display distinct constellations of somatic genetic aberrations. Epistatic interactions (ie the interplay between genetic aberrations) are likely to play pivotal roles not only in terms of tumourigenesis and disease progression, but also in response to therapeutic interventions. In this review, we discuss the challenges posed by the complexity of tumour genomes and epistatic interactions, and approaches for harnessing the wealth of genetic information on human cancers for the implementation of precision medicine.
authors.affiliation: Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY, 10065, USA.
authors.forename: Britta
authors.initials: B
authors.lastname: Weigelt
authors.forename: Jorge S
authors.initials: JS
authors.lastname: Reis-Filho
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000235:genetics*; D055808:Drug Discovery; D044127:Epigenesis, Genetic; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D023281:Genomics / Q000379:methods; D006801:Humans; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D010641:Phenotype; D057285:Precision Medicine; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor
keywords: epistasis; genetic interaction; genotype; massively parallel sequencing; mutation; precision medicine; targeted therapy